The Center of Cancer Systems Biology (CCSB) St. Elizabeth's Medical Center, Tufts Univ School of Med (TUSM), brings together diverse researchers from biological, mathematical, physical and clinical backgrounds to better understand the molecular and tissue-level events underlying cancer evolution and development. In the three years since its founding the CCSB has matured into a well-established, deeply interactive and multidisciplinary cancer group which it is becoming an internationally competitive research and training facility and research data repository in cancer systems biology Tufts CCSB has already been the recipient of two federally funded multidisciplinary Program Project Grants on carcinogenesis. Each combines mathematical and computational modeling with state-of the art experimental cancer biology. The first is a NASA Specialized Center of Research (NSCOR) funded to study risk of solid tumor carcinogenesis from space radiafion exposure ($10 Million; PI Dr. HIatky). The second is a DOE-funded center to study carcinogenesis risk following low-dose radiation exposure from background radiation ($7.5 million to Dr. HIatky and 1 million to Dr. Hahnfeldt for mathematical analysis of this issue). Clearly, both the PI and the Center are well-versed in running large program grants on carcinogenesis. Funding of this ICBP application would provide an opportunity to connect this established CCSB with the national networks of ICBP-funded Centers around the country also embarking on predictive cancer modeling and thereby contribute to the NCI directed goals of this Program. Nicolaos Madias, MD, Director of Medicine, SEMC, TUSM made deliberate strategic decisions in establishing the CCSB, recruiting Dr. HIatky as director, and the dedication of laboratory research space and computing resources, as well as the subsequent expansion of her group, represents a major institutional investment and continuing commitment to innovative, cuffing edge cancer research. SEMC has backed up this research commitment with a massive expansion plan being implemented for its clinical services at the Oncology Center, involving an additional 8,000 sq ft for Rad One and an additional 8,000 sq ft for Medical Oncology (see support letter Dr. Madias). The breadth and depth of SEMC's commitment to this long-term strategic set of goals is clear. The continuing strength of the intellectual, academic, and training environment is reinforced by Research faculty as well as clinical training appointments through TUSM.